Differences in Distribution and Detection Rate of the [68Ga]Ga-PSMA Ligands PSMA-617, -I&T and -11—Inter-Individual Comparison in Patients with Biochemical Relapse of Prostate Cancer

The biochemical relapse of prostate cancer is diagnostically challenging but of high clinical impact for subsequent patient treatment. PET/CT with radiolabeled PSMA ligands outperforms conventional diagnostic methods in the detection of tumor recurrence. Several radiopharmaceuticals were and are available for use. The aim of this study was to investigate whether the routinely applied [68Ga]Ga-PSMA ligands PSMA-617, -I&T and -11 (HBED-CC) differ in physiological and pathological distribution, or in tumor detection rate. A retrospective evaluation of 190 patients (39 patients received PSMA-617, 68 patients PSMA-I&T and 83 patients PSMA-11) showed significant differences in tracer accumulation within all organs examined. The low retention within the compartments blood pool, bone and muscle tissue is a theoretical advantage of PSMA-11. Evaluation of tumor lesion uptake and detection rate did not reveal superiority of one of the three radiopharmaceuticals, neither in the whole population, nor in particularly challenging subgroups like patients with very low PSA levels. We conclude that all three [68Ga]Ga-PSMA ligands are equally feasible in this clinically important scenario, and may replace each other in case of unavailability or production restrictions.

Individualized VDJ recombination predisposes the available Ig sequence space

The process of recombination between variable (V), diversity (D), and joining (J) immunoglobulin (Ig) gene segments determines an individual's naive Ig repertoire and, consequently, (auto)antigen recognition. VDJ recombination follows probabilistic rules that can be modeled statistically. So far, it remains unknown whether VDJ recombination rules differ between individuals. If these rules differed, identical (auto)antigen-specific Ig sequences would be generated with individual-specific probabilities, signifying that the available Ig sequence space is individual specific. We devised a sensitivity-tested distance measure that enables inter-individual comparison of VDJ recombination models. We discovered, accounting for several sources of noise as well as allelic variation in Ig sequencing data, that not only unrelated individuals but also human monozygotic twins and even inbred mice possess statistically distinguishable immunoglobulin recombination models. This suggests that, in addition to genetic, there is also nongenetic modulation of VDJ recombination. We demonstrate that population-wide individualized VDJ recombination can result in orders of magnitude of difference in the probability to generate (auto)antigen-specific Ig sequences. Our findings have implications for immune receptor–based individualized medicine approaches relevant to vaccination, infection, and autoimmunity.

Spiral gradient echo versus cartesian turbo spin echo imaging for sagittal contrast-enhanced fat-suppressed T1 weighted spine MRI: an inter-individual comparison study

Objectives: To compare a novel 3D spiral gradient echo (GRE) sequence with a conventional 2D cartesian turbo spin echo (TSE) sequence for sagittal contrast-enhanced (CE) fat-suppressed (FS) T1 weighted (T1W) spine MRI. Methods: In this inter-individual comparison study, 128 patients prospectively underwent sagittal CE FS T1W spine MRI with either a 2D cartesian TSE (“TSE”, 285 s, 64 patients) or a 3D spiral GRE sequence (“Spiral”, 93 s, 64 patients). Between both groups, patients were matched in terms of anatomical region (cervical/thoracic/lumbar spine and sacrum). Three readers used 4-point Likert scales to assess images qualitatively in terms of overall image quality, presence of artifacts, spinal cord visualization, lesion conspicuity and quality of fat suppression. Results: Spiral achieved a 67.4% scan time reduction compared to TSE. Interreader agreement was high (alpha=0.868-1). Overall image quality (4;[3,4] vs 3;[3,4], p<0.001 – p=0.002 for all readers), presence of artifacts (4;[3,4] vs 3;[3,4] p=0.027 – p=0.046 for all readers), spinal cord visualization (4;[4,4] vs 4;[3,4], p<0.001 for all readers), lesion conspicuity (4;[4,4] vs 4;[4,4], p=0.016 for all readers) and quality of fat suppression (4;[4,4] vs 4;[4,4], p=0.027 – p=0.033 for all readers), were all deemed significantly improved by all three readers on Spiral images as compared to TSE images Conclusion: We demonstrate the feasibility of a novel 3D spiral GRE sequence for improved and rapid sagittal CE FS T1W spine MRI. Advances in knowledge: A 3D spiral GRE sequence allows for improved sagittal CE FS T1W spine MRI at very short scan times.

APEKS - a method of making decisions

The APEKS method was developed in the 1970s. It has a wide range of applications for making a decision. The article describes the APEKS method, which is a multi-criteria method and consists of 10 steps. The application of this method was presented in the example of car selection. The problem of choosing a passenger car was analyzed taking into account 6 evaluation criteria: fuel consumption, power, price, annual operating costs, aesthetic values, and utility values. Following the APEKS method, the analysis was completed with the selection of the best variant, using the forced decision method, consisting of an individual comparison of all criteria with one another. The APEKS variant is used for this, which has all the best features of the variants to choose from. This indicates that APEKS is an idealized and fictional variant.

Stage-Dependent Within-Individual Comparison Reveals SIV-Specific Activation/Exhaustion Shift in Rhesus Macaques

It is challenging to trace the complicated individual-based variations of HIV-specific immunocompetence shift during the successful antiretroviral therapy (ART) era. Using eight rhesus monkeys simulating a longitudinal stage-dependent cohort (baseline-SIV acute infection-SIV suppression by ART-ART withdrawal), baseline immunocompetence monitoring for 28 days (SIV-negative stage, SN) was compared with host immunocompetence undergoing 90-day ART treatment (SIV-suppressed stage, SS) to reveal the SIV-specific immunity shift aroused by undetectable individual viral replication. During acute SIV infection for 98 days (SIV-emerged stage, SE), immune activation was compared with re-immune activation post ART for 49-day follow-up (SIV-rebounded stage, SR) to reveal the SIV-specific immune activation variation aroused by detectable individual viral replication. Individual immunocompetence was measured by co-expression of CD4, CD8, CD38, HLA-DR, CCR7, CD45RA, and PD-1 on T cells and a cytokine panel. Compared with SN, mild immune activation/exhaustion was characterized by increased CD38+ HLA-DR– CD4+/CD8+ T-cell subsets and PD-1+ memory CD4+/CD8+ T-cell subsets with three elevated cytokines (MIP-1β, IL-8, and IL-10) significantly emerged in SS. Compared with SE, SR produced more exhaustion characterized by increased PD-1+ CD4+ TCM cells and decreased PD-1+ CD4+ TEM cells with four elevated pro-inflammatory cytokines (IFN-γ, IL-1β, IL-6, and TNF-α). By such individualized stage-dependent comparison, the sustainable immune activation was found from activation/exhaustion shifted into exhaustion during the longitudinal viral persistence. Further, validated SIV accelerates host immunosenescence continuously independent of viral replication.